Drug development and CNS 1

Question 1

What was found wrong with Elixir Sulphanilamide in 1937

Answer 1

Found to be contaminated by diethylene glycol, killing 107 people

Question 2

What was found wrong with Sulfathiazole in 1941

Answer 2

Cross contamination with phenobarbital causing 300 deaths

Question 3

What was the thalidomide controvsy in 1960

Question 4

What was the thalidomide controversy in 1960

Answer 4

Was a sleeping tablet, caused 10,000-20,000 birth defects

Question 5

What’s the first stage of a clinical trial

Answer 5

Basic research target selection and pre-clinical research

Question 6

How long does the first stage of a clinical trial take

Answer 6

3- 6 years

Question 7

What is the second stage of a clinical trial

Answer 7

Clinical research phase 1 (healthy individuals)
Clinical research phase (patients for the first time)
Phase 3

Question 8

How long does the second stage take

Answer 8

6-7 years

Question 9

What’s the last stage of a clinical trial and how long does it take

Answer 9

Regulatory review (0.5 - 2 years)

Question 10

How long and how much money can you spend on a clinical trial

Answer 10

15 years and 1 billion

Question 11

What are the lead findings in drug trials

Answer 11

Exploring toxicology, safety

Question 12

How do you create a controlled environment in preclinical development

Answer 12

Providing a safety margin, defining the dose, defining a maximum dose, obtaining regulatory approval of clinical

Question 13

What does LD50 mean and when was this carried out

Answer 13

Increase the dose until 50% died, in 1920

Question 14

Now what rule is implemented

Answer 14

3R - reduce, refine, replace

Question 15

What is the default non rodent

Answer 15

Beagle

Question 16

What are the three dose groups

Answer 16

Low (no toxicity), intermediate, high

Question 17

What are the general toxicology’s

Answer 17

Clinical pathology, haematology, kidney and liver function, coagulation

Question 18

What are the goals for non-clinical safety evaluations

Answer 18

On/ off targets, reversibility, max nontoxic dose and min affective dose, identification of specific monitoring requirements

Question 19

Examples of withdrawn drugs

Answer 19

Sibutramine (appetite suppressant)
Propoxyphene
Drotecogin
Rimonabant
Hydromorphone

Question 20

Characteristics of a small molecule drug

Answer 20

Low molecular weight, chemically synthesised, well-defined structure

Question 21

Characteristics of a biological molecule and monoclonal antibodies

Answer 21

High molecular weight, derived from living organisms, large and complex structure

Question 22

How much have biologics accounted for in new medicine approvals

Answer 22

one third

Question 23

Examples of vaccines

Answer 23

HPV, COVID-19

Question 24

What are RNAi

Answer 24

interfering RNA molecules

Question 25

What are cell based therapies

Answer 25

Taking a whole cell out of a patient, modify then grow. Then inject back into patient

Question 26

Example for when cell based therapies are useful

Answer 26

Children with acute lymphoblastic leukemi

Question 27

Example of when cell based therapies are useful

Answer 27

Children with acute lymphoblastic leukaemia

Question 28

What is the phase 1 dose

Answer 28

Minimum anticipated biological effect

Question 29

What is immunotherapy

Answer 29

A form of cancer treatment, uses immune system to attack cancer cells

Question 30

What do checkpoint inhbitors do

Answer 30

Release natural brake on your immune system so that immune cells called t cells recognise and attack tumors

Question 31

What do checkpoint inhbitors do

Answer 31

Release natural brake on your immune system so that immune cells called t cells recognise and attack tumours

Question 32

What is CAR T cell therapy

Answer 32

Scientists engineer a patient's own immune cells to make a new protein

Question 33

Who discovered nitrous oxide and when

Answer 33

Horace Wells in the mid 1800s

Question 34

How are general anaesthetics characterised

Answer 34

By how the chemicals are administered to induce a state of anaesthesia

Question 35

What are chemical inhalational anaesthetics and example

Answer 35

Nitrous oxide and through the lungs

Question 36

What are intravenous anaesthetics and example

Answer 36

Administered directly into the circulation system and steroids, barbitruates and halogenated hydrocarbions

Question 37

Whay are ethers and chloroform not used anymore

Answer 37

They can vapourise at low temperatures and are highly explosive and flammable

Question 38

What are physical anesthetics

Answer 38

Low pressure (atmospheric) and cold temperatures such as hypothermia

Question 39

What is the lipid theory of general anaesthetics

Answer 39

The idea that somehow these drugs cause membrane expansion

Question 40

What is the Meyer- overton rule

Answer 40

The anaesthetic effect was considered proportional to the molar concentratiof the agent in lipid

Question 41

What are the problems with the lipid theory of general anaesthetics

Answer 41

There's no temperature effect, no binding sites, no loss of activity with homologoys series of lipophilic compounds and no increase in GABA A

Question 42

What do low concentrations of volatile gases activate

Answer 42

Two pore domain K channels

Question 43

What does ketamine and nitrous oxide block

Answer 43

NDMS receptors

Question 44

What does an increase in inhibitory neurotransmission through GABA A receptors lead to

Answer 44

Inhibition in neural networks

Question 45

What does an increase in inhibitory neurotranmission of reticular formation lead to

Answer 45

Unconciousness

Question 46

What does an increase in inhibitory neurotransmission through the hippocampus lead to

Answer 46

Short term memory loss/ amnesia

Question 47

What happens as the concetration of anesthetics is increased

Answer 47

Inhibition in the CNS, leading to loss of motor control, absejce of artificial respiration leading to death

Question 48

4 stages of anaesthesia

Answer 48

1. Analgesia 2. Excitement state 3. Surgical aneasthesia 4. Medullary paralysis

Question 49

What are the ideal conditons from anaestheia

Answer 49

Rapid induction and loss of conciousnes, good analgesia, muscle relaxation, rapid recovy

Question 50

Advantages of intravenous anaesthetics

Answer 50

Easy to administer, rapid induction, short duration of action

Question 51

Disdvantages of intravenous anaesthetics

Answer 51

Pain at the site of infection, complex pharmacokinetics

Question 52

Disadvantages of thiopental and what is it an example of

Answer 52

A barbituate intravenous drug. It has a high lipid soluability, low therapeutic index

Question 53

Side effects of intravenous drugs

Answer 53

Respitary depression, cardiovascular deprssion

Question 54

What is ketamine

Answer 54

A dissociative anaesthetic

Question 55

What does ketamine do

Answer 55

Causes sensory loss, powerful analgesic, causes amnesia

Question 56

What are the side effects of ketamine

Answer 56

Increased CV excitement, involuntary movements, increased intracranial pressure, hallucinations, delirium, irrational behaviour

Question 57

What is ketamine used for

Answer 57

In pediatrics (with BZD) and vetinary, starting to be used for depression in adults

Question 58

Examples of inhalational anaesthetics

Answer 58

Isoflurane, desflurane and sevoflurane

Question 58

Examples of inhalational anaesthetics

Answer 58

Isoflurane, desflurane and sevoflurane

Question 59

What are anxiolytics

Answer 59

Drugs used to treat anxiety

Question 60

What are hypnotics

Answer 60

Drugs used to treat sleep disorders

Question 61

What hormone is secreted when fear response is activated

Answer 61

Cortisol

Question 62

What is a fear response characterised by

Answer 62

Defensive behaviours, autonomic reflexes, alertness, corticosteroid secretion and negative emotions

Question 63

Examples of anxiety disorders

Answer 63

Panic disorder, phobias, social anxiety, PTSD, OCD, generalised anxiety

Question 64

Treatments for anxiety

Answer 64

Benzodiazepines and barbiturates, antidepressants, antiepileptics and antipsychotics

Question 65

Examples of animal models of anxiety

Answer 65

Elevated cross test, the light/ dark box

Question 66

What are GABA A receptors targets for

Answer 66

Anxioltyics and hypnotics

Question 67

What is a GABA A receptor

Answer 67

A lingand gated ion channel

Question 68

What is a GABA B receptor

Answer 68

A g coupled receptor

Question 69

What is picrotoxin

Answer 69

A non competitive agonist of the GABA receptor by blocking the pore

Question 70

What is the second site at the GABA receptor known as

Answer 70

The positive allosteric regulator

Question 71

What does the allosteric modulator do

Answer 71

Doesn't activate receptor on its own, it modifies the behaviour of the receptor when agonist is bound to the orthostatic site

Question 72

What are the physiological effects of the benzodiapene agonists

Answer 72

Sedation, hypnosis, anterograde amnesia, anti- convulsant, reduction of muscle tone

Question 73

What are the adverse effects of benzodiapene agonists

Answer 73

Decreased tolerance due to increased exposure, misuse, physical dependance,

Question 74

What is epivario useful for

Answer 74

Post traumatic stress disorder- prevents the consolidation of the memory